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Observational Study
. 2025 Sep;18(9):e018370.
doi: 10.1161/CIRCIMAGING.125.018370. Epub 2025 Jul 16.

Assessing LV Contractility Identifies Populations With Preserved Ejection Fraction at Risk of Adverse Heart Failure Outcomes

Sam Straw  1 , Oliver I Brown  1 , Charlotte A Cole  2 , Judith E Lowry  2 , Marcella Conning-Rowland  1 , Stephe Kamalathasan  2 , Sushma Datla  3 , Maria F Paton  1 , Ruth Burgess  2 , Michael Drozd  1 , Thomas A Slater  1 , Samuel D Relton  4 , Eylem Levelt  1   5 , Klaus K Witte  1 , Mark T Kearney  1 , Richard M Cubbon  1 , John Gierula  1
Affiliations
Observational Study

Assessing LV Contractility Identifies Populations With Preserved Ejection Fraction at Risk of Adverse Heart Failure Outcomes

Sam Straw et al. Circ Cardiovasc Imaging. 2025 Sep.

Abstract

Background: Left ventricular ejection fraction (LVEF) is an essential tool for heart failure (HF) assessment but is limited by load dependence. Additional tools are needed to risk-stratify normal LVEF populations. We aimed to assess the prognostic value of systolic blood pressure-indexed left ventricular end-systolic volume ratio, or cardiac contractility index (CCI).

Methods: In a prospective observational cohort study of people newly diagnosed with HF, we defined characteristics and outcomes associated with LVEF and CCI, including after stratification into HF with reduced ejection fraction or HF with preserved ejection fraction. We used UK Biobank to assess whether CCI is associated with subclinical myocardial dysfunction and incident HF.

Results: In people with HF, mortality increased over tertiles of declining CCI (P<0.001). Within the HF with preserved ejection fraction group, below-median CCI was associated with distinct clinical characteristics and an all-cause mortality risk approximately twice that of those with above median CCI (observed event rate 17.3/100 patient-years versus 8.8/100 patient-years; P<0.001), similar to those with HF with reduced ejection fraction. Modeled as continuous variables, there was a curvilinear relationship between mortality across the detected range of CCI, while there was no clear association with mortality risk across a wide range of LVEF (20%-55%). In UK Biobank for participants without HF and normal LVEF, below-median CCI was associated with ≈33% increased risk of incident HF (adjusted hazard ratio, 1.33 [1.01-1.75]; P=0.043). Decreasing CCI was also associated with lower myocardial contractility defined using global radial and circumferential strain.

Conclusions: CCI is a simple, noninvasive, relatively afterload-independent method to stratify HF risk in populations with normal LVEF. Its simplicity means CCI could be applied to existing clinical trial data sets or used be as an inclusion criterion in future randomized controlled trials.

Keywords: blood pressure; heart failure; humans; prognosis; stroke volume.

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Conflict of interest statement

Dr Straw has received speaker fees, honoraria, and a research grant from AstraZeneca. Dr White has received personal fees from Medtronic, Cardiac Dimensions, Novartis, Abbott, BMS, Pfizer, and Bayer, and has received an unconditional research grant from Medtronic. Dr Kearney has received personal fees and a research grant from AstraZeneca. Dr Gierula has received personal fees from Abbott, Medtronic, and MicroPort, and has received an unrestricted research grant from Medtronic. The other authors report no conflicts.

Figures

Figure 1.
Figure 1.
The relationship between left ventricular ejection fraction (LVEF) and cardiac contractility index (CCI) in the NICE-CHF (National Institute for Clinical Excellence Guidelines on Chronic Heart Failure) cohort. A, Scatter plots of LVEF and CCI and (B) bar charts showing the frequency of individuals with heart failure (HF) and reduced LVEF and low CCI (dark red), reduced LVEF and high CCI (light red), preserved LVEF and low CCI (dark gray) and preserved LVEF and high CCI (light gray). HFpEF indicates heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; r, correlation coefficient; and R2; coefficient of determination.
Figure 2.
Figure 2.
Kaplan-Meier plots of all-cause mortality divided by tertiles of left ventricular ejection fraction (LVEF) and cardiac contractility index (CCI) in the NICE-CHF (National Institute for Clinical Excellence Guidelines on Chronic Heart Failure) cohort.
Figure 3.
Figure 3.
Restricted cubic splines displaying incidence rate ratios (IRR) and 95% CIs of all-cause mortality across left ventricular ejection fraction (LVEF) and cardiac contractility index (CCI) in the NICE-CHF (National Institute for Clinical Excellence Guidelines on Chronic Heart Failure) cohort.
Figure 4.
Figure 4.
Kaplan-Meier plot of all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) who had cardiac contractility index (CCI) below or above the median value in the NICE-CHF (National Institute for Clinical Excellence Guidelines on Chronic Heart Failure) cohort. Survival distributions between groups compared by Log-Rank test.
Figure 5.
Figure 5.
Scatter plots of cardiac contractility index (CCI) compared to global radial, circumferential, and longitudinal strain in the UK Biobank cohort. LV indicates left ventricular; r, correlation coefficient; and R2; coefficient of determination.
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